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United States Patent | 5,731,190 |
Wickham ,   et al. | March 24, 1998 |
A recombinant adenovirus comprising a chimeric penton base protein, which includes a nonpenton base sequence, and a therapeutic gene, a method of gene therapy involving the use of such adenovirus, and adenoviral transfer vectors for the generation of such recombinant adenovirus are provided.
Inventors: | Wickham; Thomas J. (Gaithersburg, MD); Kovesdi; Imre (Rockville, MD); Brough; Douglas E. (Olney, MD); McVey; Duncan L. (Derwood, MD); Bruder; Joseph T. (New Market, MD) |
Assignee: | GenVec, Inc. (Rockville, MD) |
Appl. No.: | 709515 |
Filed: | September 6, 1996 |
Current U.S. Class: | 435/320.1; 435/69.7; 530/350 |
Intern'l Class: | C12N 015/86; C12N 015/62; C12N 015/34; A61K 048/00 |
Field of Search: | 514/44 435/69.7,172.1,235.1,320.1,5,172.3 935/57 424/93.2 530/350 |
4578079 | Mar., 1996 | Ruoslahti et al. | 623/11. |
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5204445 | Apr., 1993 | Plow et al. | 530/326. |
5223409 | Jun., 1993 | Ladner et al. | 435/69. |
5332567 | Jul., 1994 | Goldenberg | 424/1. |
5403484 | Apr., 1995 | Ladner et al. | 435/235. |
5443953 | Aug., 1995 | Hansen et al. | 424/1. |
5521291 | May., 1996 | Curiel et al. | 530/391. |
5559099 | Oct., 1996 | Wickham et al. | 514/44. |
5571698 | Nov., 1996 | Ladner et al. | 435/69. |
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Karyan et al., Virology, 202, 782-785 (1994). Database WPI, Week 9017, Derwent Publications Ltd., AN 90-129060/17 (JP 2,078,631 abstract). Albiges-Rizo et al., "Human adenovirus serotype 3 fiber protein. Comparison of native and recombinant proteins," J. Biol. Chem., 266(6), 3961-3967 (1991). Bai et al., "Mutations That Alter an Arg-Gly-Asp (RGD) Sequence in the adenovirus Type 2 Penton Base Protein Abolish Its Cell-Rounding Activity and Delay Virus Reproduction in Flatt Cells," Journal of Virology, 67(9), 5198-5205 (1993). Ball-Goodrich et al., "Parvoviral Target Cell Specificity: Acquisition of fibrotropism by a mutant of the lymphotropic strain of minute Virus involves multiple amino acid substitutions within the capsid," Virology, 184, 175-186 (1991). Cotten et al., "High-Efficiency Receptor-Mediated Delivery of Small and Large (48 Kilobase) Gene Constructs Using the Endosome-Disruption Activity of Defective or Chemically Inactivated Inactivated Adenovirus Particles," Proc. Natl. Acad. Sci, USA, 89, 6094-6098 (1992). Curiel et al., "High-Efficiency Gene Transfer Mediated By Adenovirus Coupled to DNA-Polylysine Complexes," Human Gene Therapy, 3, 147-154 (1992). Greber et al., "Stepwise Dismantling of Adenovirus 2 During Entry Into Cells," Cells, 75, 477-486 (1993). Hong et al., "The amino terminus of the adenovirus fiber protein encodes the nuclear localization signal," Virology, 185(2), 758-767 (1991). Horvath et al., "Nonpermissivity of Human Periphral Blood Lymphocytes to Adenovirus Type 2 Infection," Journal of Virology, 62(1), 341-345 (1988). Komoriya et al., "The Minimal Essential Sequence for a Major Cell Type-Specific Adhesion Site (CSI) Within the Alernatively Spliced Type III Connected Segment Domain of Fiberonectin Is Leucine-Asparitic Acid-Valine," The Journal of Biological Chemistry, 266(23), 15075-15079 (1991). Mathias et al., "Muliple Adenovirus Serotypes Use .alpha.v Integrins For Infection," Journal of Virology, 68(10), 6811-6814 (1994). Nemerow et al., "Adenovirus Entry Into Host Cells: A Role For .alpha..sub.v Integrins," Trends In Cell Biology, 4, 52-55 (1994). Nemerow et al., "The Role of .alpha.v Integrins In Adenovirus Infection," Biology of Vitronectins and Their Receptors, Elsevier Science Pub., Preissner et al., eds., 177-184. Novelli et al., "Deletion analysis of functional domains in Baculovirus-expressed Adenovirus type 2 fiber," Virology, 185(1), 365-376 (1991). Silver et al., "Interaction of Human Adenovirus Serotype 2 With Human Lymphoid Cells," Virology, 165, 377-387 (1988). Stewart et al., "Difference Imaging of Adenovirus: Bridging The Resolution Gap Between X-Ray Crystallography And Electron Microscopy," The EMBO Journal, 12(7), 2589-2599 (1993). Wickham et al., "Integrins .alpha..sub.v .beta..sub.3 and .alpha..sub.v .beta..sub.5 Promote Adenovirus Internalization But Not Virus Attachment," Cell, 73, 309-319 (1993). Wickham et al., "Targeting of adenovirus penton base to new receptors through replacement of its RGD motif with other receptor-specific peptide motifs," Gene Ther., 2(10), 750-756 (1995). |
__________________________________________________________________________ SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 24 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: ArgGlyAsp (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: LysGlnAlaGlyAsp 15 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: GluIleLeuAspVal 15 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: AsnProXaaTyr 1 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 65 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 51..65 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: CTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGAATTCCCCTTAGTATGCGG56 MetArg 1 CGCGCGGCG65 ArgAlaAla 5 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: MetArgArgAlaAla 15 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 65 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 51..65 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: CTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGTATTCCCCTTAGTATGCGG56 MetArg 1 CGCGCGGCG65 ArgAlaAla 5 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: MetArgArgAlaAla 15 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..30 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: GACATGAACGATACTAGTGCCACACGGGCT30 AspMetAsnAspThrSerAlaThrArgAla 1510 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: AspMetAsnAspThrSerAlaThrArgAla 1510 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 48 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..48 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: GACATGAACGATCATGCCATTCGCGGCGACACCTTTGCCACACGGGCT48 AspMetAsnAspHisAlaIleArgGlyAspThrPheAlaThrArgAla 151015 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: AspMetAsnAspHisAlaIleArgGlyAspThrPheAlaThrArgAla 151015 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 52 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: AAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGAATTCCCCTTA52 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 25 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: CTGGCGGGCGCGCCAAAATCTGGTT25 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: AAAACTAGTGCCACACGGGCTGAGGA26 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: AAAACTAGTATCGTTCATGTCCTCCA26 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 68 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 3..68 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: AAACTAGTGGAGGATGCTCTTTTGGCCGCGGCGACATTCGCAACTGC47 ThrSerGlyGlyCysSerPheGlyArgGlyAspIleArgAsnCys 151015 GGCGGCCTGCAGTCTAGAAAA68 GlyGlyLeuGlnSerArgLys 20 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: ThrSerGlyGlyCysSerPheGlyArgGlyAspIleArgAsnCysGly 151015 GlyLeuGlnSerArgLys 20 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 41 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: AAACTAGTGGAGGATGCTCTTTTGGCCGCGGCGACATTCGC41 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 42 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: TTTTCTAGACTGCAGGCCGCCGCAGTTGCGAATGTCGCCGCG42 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 110 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 3..110 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: AAACTAGTGGAGGAGACGAGCTCCCACAGCTCGTGACTCTCCCACAC47 ThrSerGlyGlyAspGluLeuProGlnLeuValThrLeuProHis 151015 CCAAACCTCCACGGTCCAGAGATTCTCGACGTGCCATCTACTGGCGGC95 ProAsnLeuHisGlyProGluIleLeuAspValProSerThrGlyGly 202530 CTGCAGTCTAGAAAA110 LeuGlnSerArgLys 35 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: ThrSerGlyGlyAspGluLeuProGlnLeuValThrLeuProHisPro 151015 AsnLeuHisGlyProGluIleLeuAspValProSerThrGlyGlyLeu 202530 GlnSerArgLys
35 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 65 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: AAACTAGTGGAGGAGACGAGCTCCCACAGCTCGTGACTCTCCCACACCCAAACCTCCACG60 GTCCA65 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 60 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: TTTTCTAGACTGCAGGCCGCCAGTAGATCGCACGTCGAGAATCTCTGGACCGTGGAGGTT60 __________________________________________________________________________